Our study aimed to determine if chemotherapy administration based on the 21-gene Oncotype DX Recurrence Score (RS) in men with hormone receptor positive (HR+) Her2 negative (Her2-) lymph node positive(LN+) breast cancers (BC) impacted overall survival (OS). We conducted a retrospective cohort study on adult men and women with HR+ Her2-, 1–3 axillary LN + BC, with a valid oncotype DX RS assay, diagnosed between the years 2004–2020, using the National Cancer Database. RS risk categories were defined as low risk: 0–13, intermediate risk:14–25, and high risk: ≥26. Of the 77,820 patients included in the study, 900 (1.2

BACKGROUND:Differences in patient and tumor characteristics among American Indian/Alaska Native (AI/AN) and non-Hispanic White (NHW) breast cancers (BC) adversely impact overall survival (OS) in AI/AN. The aims of this study were to: 1) investigate disparities in treatment of early triple negative breast cancers (TNBC); 2) assess differences in OS. METHODS:A hospital-based, retrospective cohort study using the National Cancer Database included AI/AN and NHW women, 18 years or older, diagnosed with TNBC between 2010 and 2019, stages I-III. Propensity score matching (1:3 ratio) was used for age, year, and analytic stage at diagnosis. RESULTS:A total of 489 AI/AN and 1465 available matched NHW women with TNBC were analyzed. Time to first treatment (TFT) was significantly longer for AI/AN (P = .005). Multivariate analysis revealed that longer TFT was associated with only higher Charlson-Deyo Score (CDS) (P = .014) and nonprivate insurance (P < .001), but not race (P = .568). Overall treatment compliance was similar (AI/AN - 89.6% vs. NHW - 92.2%, P = .074). Compliance was significantly associated with only insurance status (P < .001). On multivariate analysis OS did not differ by race (P = .687, HR = 1.06; 95% CI: 0.79-1.44). Cancer stage, CDS, insurance status, and treatment compliance were associated with worse OS. CONCLUSION:In patients with TNBC, there was no difference in TFT, compliance with recommended treatment or OS among AI/AN in comparison to White women when matched for age, stage, and year of diagnosis. In order to improve BC survival, it is important to manage comorbid conditions and improve detection of cancer at earlier stages.

Gastric cancer, a leading cause of cancer-related mortality globally, presents significant challenges in prognosis and treatment due to its heterogeneity. This study aimed to elucidate the role of mitochondrial-related genes (MRGs) in gastric cancer and develop a prognostic model. We analyzed RNA sequencing data and clinical information of 412 gastric cancer samples from The Cancer Genome Atlas (TCGA). A comprehensive list of 1136 MRGs was curated from the MitoCarta3.0 database, leading to the identification of 110 differentially expressed MRGs between gastric cancer and normal tissues. Using univariate and multivariate Cox regression analyses, we constructed the Mitochondrial-Related Risk Score (MLRScore), a prognostic model incorporating five key MRGs. The model was validated in training and testing cohorts and exhibited promising prognostic capability. Additionally, we investigated the relationship between MLRScore and immune cell infiltration, somatic mutations, tumor mutation burden (TMB), and response to chemotherapy. The MLRScore was found to correlate with distinct immune landscapes and chemotherapeutic sensitivities, suggesting its potential utility in guiding personalized treatment strategies. Our study not only provides a novel tool for prognostic assessment in gastric cancer but also underscores the importance of mitochondrial dynamics in tumor biology and patient stratification.

As a commonly used material that contacts food, polyethylene glycol terephthalate (PET) may interact with food, and since certain components can migrate, this has become a food safety concern. This study aims to investigate the genotoxicity of PET acetic acid migration solution and its toxic mode of action using an in vivo multi-endpoint genotoxicity evaluation system and quantitative liver proteomics analysis. Forty-eight male Sprague-Dawley rats were randomly divided into eight groups: the PET acetic acid migration solution group, the acetic acid group, the phosphate-buffered saline (PBS) control group, the N-ethyl-N-nitrosourea (ENU) positive control group, and their corresponding satellite groups. PBS and ENU were administered by gavage, while the PET acetic acid migration solution and acetic acid were administered orally in the drinking water. The exposure duration was 35 days, followed by a recovery period of 15 days. The PET acetic acid migration solution can cause heart, liver, and kidney injury in rats. On the 15th day, mutations were seen in the Pig-a gene test. On the 35th day, DNA damage was observed in peripheral blood and liver cells. Gene ontology (GO) analysis of the liver proteomics revealed enrichment in DNA metabolism and binding processes, while Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted the DNA replication pathway. Immunohistochemical analysis demonstrated a significant increase in 8-hydroxydeoxyguanosine (8-OHdG) and a decrease in single-stranded-binding (SSB) protein in the PET acetic acid migration solution group. In summary, the PET acetic acid migration solution has the potential to induce DNA damage, possibly by inhibiting DNA replication and DNA repair pathways. However, the likelihood of genetic toxicity is low.

2-Methylfuran (2-MF) is an important member of the furan family generated during food thermal processing. An in-vivo multiple endpoint genotoxicity assessment system was applied to explore the genotoxic mode of action and threshold of 2-MF. Male Sprague–Dawley rats received 2-MF by oral gavage at doses of 0.16, 0.625, 2.5, and 10 mg/kg.bw/day for 120 days. An additional 15 days were granted for recovery. The Pig-a gene mutation frequency of RET and RBC showed significant increases among the 2-MF groups on day 120. After a 15-day recovery period, the Pig-a gene mutation frequency returned to levels similar to those in the vehicle control. The tail intensity (TI) values of peripheral blood cells at a dose of 10 mg/kg.bw/day significantly increased from day 4 and remained at a high level after the recovery period. No statistical difference was found in the micronucleus frequency of peripheral blood between any 2-MF dose group and the corn oil group at any timepoint. 2-MF may not induce the production of micronuclei, but it could cause DNA breakage. It could not be ruled out that 2-MF may accumulate in vivo and cause gene mutations. Hence, DNA, other than the spindle, may be directly targeted. The mode of action of 2-MF may be that it was metabolized by EPHX1 to more DNA-active metabolites, thus leading to oxidative and direct DNA damage. The point of departure (PoD) of 2-MF-induced genotoxicity was derived as 0.506 mg/kg bw/day.

e13736 Background: There are significant differences in patient and tumor characteristics among AI/AN and NHW breast cancers (BC) which adversely impact overall survival in AI/AN. Prior studies have also shown higher Mortality: Incidence ratio for BCs in AI/AN as compared to NHW. The aims of this study are to 1) investigate disparities in adjuvant treatment of TNBC between the two races adjusting for age, stage, and year of diagnosis; and 2) Assess differences in OS. Methods: This was a hospital based, retrospective cohort study using the National Cancer Database. AI/AN and NHW women with TNBC, greater than or equal to 18 years of age, diagnosed with BC between the years 2010 through 2019, stages I, II, and III were included. Propensity score matching in a 1:3 ratio was used for age, year, and analytical stage at diagnosis. Primary endpoint was time to first treatment and compliance with recommended treatment. Secondary endpoint was OS. Results: A total of 489 AI/AN and 1465 matched NHW women with TNBC were identified. AI/AN women traveled longer distances for cancer care (p<.01), resided in lower median income zip codes at the time of diagnosis (p<.001), had a higher Charlson-Deyo (CD) comorbidity score (p<.001), and were less likely to have private insurance (p<.001). There was no difference in the rates of chemotherapy, surgery, and radiation therapies that were recommended and received by the two races. Time to first treatment was significantly longer for AI/AN as compared to NHW women (Mean ± SD: 35 ± 27 days vs. 39 ±27 days; p=.005). Multivariable analysis revealed that longer time to first treatment was associated with only higher CD score (p=.013) and non-private insurance (p=.027), but no longer associated with race (p=.324). Compliance with recommended treatment was similar between AI/AN and NHW women (93.5% vs 92.9%, p=.096). Compliance was significantly associated with only insurance status (p < .001) with Medicare/Medicaid having the lowest compliance. OS did not differ by race (p=.299, HR=1.132; 95% CI: 0.90-1.43). Cancer stage, CD score, insurance status, and treatment compliance were associated with worse OS. Conclusions: In patients with TNBC, there was no difference in time to treatment, compliance with recommended treatment or OS among AI/AN in comparison to White women when matched for age, stage, and year of diagnosis. Medicare/Medicaid insurance was associated with prolonged time to treatment, lower compliance with recommended treatment and decreased survival when compared with other insurances. Higher comorbidities adversely impacted time to treatment and overall survival. In order to improve BC mortality, it is important to manage comorbid conditions and improve detection of cancer at earlier stages. Prospective studies comparing outcomes by race are needed to confirm these findings.

Background Breast cancer (BC) death rates in the USA have not significantly declined for American Indians (AIs) in comparison to Whites. Our objective was to determine whether Medicaid Expansion as part of the Affordable Care Act led to improved BC outcomes for AIs relative to Whites. Patients and Methods Using the National Cancer Database, we conducted a retrospective cohort study. Included were BC patients who were AI and White; 40 to 64 years of age; diagnosed in 2009 to 2016; lived in states that expanded Medicaid in January 2014, and states that did not expand Medicaid. Our outcomes were stage at diagnosis, insurance status, timely treatment, and 3-year mortality. Results There were 359,484 newly diagnosed BC patients, 99.49% White, 0.51% AI. Uninsured rates declined more in the expansion states than in the nonexpansion states (OR = 0.44, 95% CI: 0.15-0.97, P < 0.001). Lower rates of Stage I BC diagnosis was found in AIs compared to Whites (46.58% vs. 55.33%, P < .001); these differential rates did not change after Medicaid expansion. Rates of definitive treatment initiation within 30 days of diagnosis declined after Medicaid expansion (P < .001); there was a smaller decline in the expansion states (OR 1.118, 95% CI: 1.09, 1.15, P < .001). Three year mortality was not different between expansion and nonexpansion states post Medicaid expansion. Conclusions In newly diagnosed BCs, uninsured rates declined more in the states that expanded Medicaid in January 2014. Timely treatment post Medicaid expansion declined less in states that expanded Medicaid. There was no differential benefit of Medicaid expansion in the 2 races.

Differences in Breast Cancers among American-Indians and Whites in the United States Background - The United States has made substantial progress in improving breast cancer (BC) outcomes over the years, but unfortunately, this improvement has not impacted all races equally. BC death rates have not improved significantly for American Indian (AI) women, whereas, it significantly decreased for White women. In addition, AI women were more likely to be diagnosed at a younger age with a late-stage disease. We sought to determine the reasons for these disparities. Methods - This is a retrospective cohort study using a hospital registry database (the National Cancer Data Base) (NCDB). We identified female AIs and non-Hispanic Whites in the US diagnosed with BC between the years 2004 and 2016. We compared patient and tumor characteristics between the 2 groups and its effect on age and stage at diagnosis. We also determined hazard ratios (HRs) for overall survival using Cox regression models, both before and after adjustment for covariates. Results – Data on 6,866 AIs and 1,987,324 White women diagnosed with BC were analyzed. The mean (SD) age at diagnosis was significantly younger for AI than for White women (57.72 ± 12.23 vs. 61.87 ± 13.21). AI women traveled double the distance to their treatment facilities, lived in lower median income zip codes, reported a higher percentage of no insurance, and higher comorbidities than Whites. Furthermore, AIs were less likely to be diagnosed with Stage 0 and I BCs, had a larger tumor size, greater number of positive lymph nodes at diagnosis, and higher proportion of triple negative and HER2-positive BCs than Whites. Whites were more likely to have other cancers diagnosed prior to or after their BC diagnosis. All the above tests for comparisons were significant (p-value < 0.001). Correlation between patient/tumor characteristics with age and stage at diagnosis was not significantly different between AIs and Whites. Unadjusted overall survival (OS) was significantly worse for AIs as compared to Whites (HR=1.07; 95% CI: 1.01-1.14, p-value = 0.025). After adjustment of all covariates including age, travel distance, median income of residential zip code, insurance status, cancer sequence, comorbidities, stage, tumor size, number of positive lymph nodes, grade, histology, and hormonal/HER2 status, OS was not significantly different between AIs and Whites (HR=1.04; 95% CI: 0.90-1.20, p-value = 0.601). Conclusion - Our study showed significant differences in patient and tumor characteristics among AI and White BC patients which adversely impacted BC outcomes in AIs. Survival was lower in AIs, but when adjusted for various covariates, the survival difference disappeared. Improvement in BC outcomes in AIs will involve not only improved and early access to screening to identify patients at younger ages and earlier stages at diagnosis, but also long term plans to provide affordable and the full spectrum of cancer care closer to home. Citation Format: Anu Gaba, Li Cao, Rebecca Renfrew, Janet Wernisch, Abe Sahmoun, Sanjay Goel, Ross Crosby. Differences in Breast Cancers among American-Indians and Whites in the United States [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-06-03.

Bisphenol AF (BPAF), as one of structural analogs of BPA, has been increasingly used in recent years. However, limited studies have suggested its adverse effects similar to or higher than BPA. In order to explore the general toxicity and genotoxicity of subacute exposure to BPAF, the novel 28-day multi-endpoint (Pig-a assay + micronucleus [MN] test + comet assay) genotoxicity evaluation platform was applied. Male rats were randomly distributed into seven main experimental groups and four satellite groups. The main experimental groups included BPAF-treated groups (0.5, 5, and 50 μg/kg·bw/d), BPA group (10 μg/kg·bw/d), two solvent control groups (PBS and 0.1% ethanol/99.9% oil), and one positive control group (N-ethyl-N-nitrosourea, 40 mg/kg bw). The satellite groups included BPAF high-dose recovery group (BPAF-HR), oil recovery group (oil-R), ENU recovery group (ENU-R), and PBS recovery group (PBS-R). All groups received the agents orally via gavage for 28 consecutive days, and satellite groups were given a recovery period of 35 days. Among all histopathologically examined organs, testis and epididymis damage was noticed, which was further manifested as blood-testis barrier (BTB) junction protein (Connexin 43 and Occludin) destruction. BPAF can induce micronucleus production and DNA damage, but the genotoxic injury can be repaired after the recovery period. The expression of DNA repair gene OGG1 was downregulated by BPAF. To summarize, under the design of this experiment, male reproductive toxicity of BPAF was noticed, which is similar to that of BPA, but its ability to induce micronucleus production may be stronger than that of BPA.

ImportanceBreast cancer (BC) death rates have not improved for American Indian/Alaska Native (AI/AN) women, whereas, it has significantly decreased for non-Hispanic White (White) women.ObjectiveDelineate the differences in patient and tumor characteristics among AI/AN and Whites with BC, and its impact on age and stage at diagnosis as well as overall survival (OS).MethodsHospital-based, cohort study using the National Cancer Database to identify female AI/AN and Whites diagnosed with BC between the years 2004 and 2016.ResultsBC in 6866 AI/AN (0.3%) and 1,987,324 Whites (99.7%) were studied. The median age at diagnosis was 58 for AI/AN and 62 for Whites. AI BC patients traveled double the distance for treatment, lived in lower median income zip codes, had a higher percentage of uninsured, higher comorbidities, lower percentage of Stage 0/I, larger tumor size, greater number of positive lymph nodes, higher proportion of triple negative and HER2-positive BC than Whites. All the above comparisons were significant, p<0.001. Association between patient/tumor characteristics with age and stage at diagnosis was not significantly different between AI/AN and Whites. Unadjusted OS was worse for AI/AN as compared to Whites (HR=1.07, 95% CI=1.01-1.14, p=0.023). After adjustment of all covariates, OS was not different (HR=1.038, 95%CI=0.902-1.195, p=0.601).ConclusionThere were significant differences in patient/tumor characteristics among AI/AN and White BC which adversely impacted OS in AI/AN. However, when adjusted for various covariates, the survival was similar, suggesting that the worse survival in AI/AN is mostly the impact of known biological, socio-economic, and environmental determinants of health.

目的:通过小鼠动物模型,观察程序性死亡受体1(programmed death 1,PD-1)抑制剂对肺脏免疫微环境、肺损伤及纤维化的影响.方法:将15只C57BL/6小鼠随机分为3组,每组5只,A组为空白对照组,B组为IgG组对照组,C组为PD-1抑制剂组,每周给药1次,共计给药6周.第7周麻醉处死小鼠,HE和Masson染色观察肺组织形态学改变和评估纤维化,免疫组化检测CD3+、CD4+、CD8+T淋巴细胞浸润情况,流式细胞术检测细胞因子(IL-4、IL-6、IL-17A、TNF-α、TGF-β1、IFN-γ)水平,并检测肺组织羟脯氨酸含量.结果:A组和B组未见明显的肺损伤,C组可见肺泡间隔增厚、间质中炎症细胞浸润增加.A组和B组未见明显纤维化,C组可见肺间质胶原纤维沉积,半定量分析结果显示A、B、C组胶原容积分数(collagen volume fraction,CVF)分别为4.30％±1.06％、5.10％±1.37％、10.70％±2.83％,C组的CVF高于A组和B组(P<0.01);A组和B组的羟脯氨酸含量相似,C组羟脯氨酸含量比A组和B两组增高(P<0.01).与A组和B组比较,C组的CD3+T淋巴细胞浸润显著增加,主要是以CD8+T淋巴细胞浸润为主,CD4+T淋巴细胞浸润不明显,C组的IL-6、TGF-β1水平高于A组和B组(P<0.01).结论:PD-1抑制剂促进CD8+T淋巴细胞向肺组织浸润,通过诱导免疫炎症反应导致肺损伤及纤维化.

Objective:To explore the potential mechanism of PD-1 inhibitor P on RIMI from the perspective of immune microenvironment.Methods:To establish a mouse model of radiation-induced myocardial injury (RIMI), twenty C57BL/6 mice were randomly divided into 4 groups, 5 in each group. Group A was the healthy control group; Group B was the PD-1 inhibitor group; Group C was the simple irradiation group, with a heart irradiation of 15 Gy; Group D was the irradiation+ PD-1 inhibitor group. One month after irradiation, the mice were anesthetized and sacrificed. The morphological changes of myocardial tissues were observed by HE staining. The myocardial fibrosis was assessed by Masson staining. CD 3+ , CD 3+ CD 4+ , CD 3+ CD 8 lymphocyte subsets and cytokines (IL-4, IL-6, IL-17A, TNF-α, TGF-β 1 and INF-γ) levels were determined by flow cytometry. The apoptosis rate of myocardial cells was detected by TUNE. Results:One month after irradiation, there was no obvious myocardial fibrosis in group B, and collagen fibers were distributed in the interstitium of myocardial cells in groups C and D. Semi-quantitative analysis results showed that the myocardial collagen volume fraction (CVF) of groups A, B, C and D were (1.97±0.36)%, (2.83±1.03)%, (5.39±0.77)% and (7.72±1.43)%, respectively. The CVF between group A and group B was similar ( P=0.314), and the differences in CVF between the other groups were statistically significant (all P<0.05). Compared with group A, the absolute value and percentage of CD 3+ T lymphocytes were significantly increased in groups B, C and D (all P<0.01). The values in group D were significantly higher than those in group B and group C (all P<0.01); The absolute value and percentage of CD 3+ CD4 T lymphocytes were similar among four groups (all P>0.05); The absolute value and percentage of CD 3+ CD 8 T lymphocytes in group D were significantly higher than those in groups A, B and C (all P<0.001). The expression levels of IL-6, IL-17A, and TGF-β 1 in group D were significantly higher compared with those in groups A, B and C (all P<0.001). The apoptotic index was gradually increased in four groups, and the differences in apoptotic index among four groups were statistically significant (all P<0.001). Conclusion:PD-1 inhibitors can aggravate RIMI by promoting myocardial immune inflammatory response.

Purpose: American Indians (AIs) constitute the single largest racial minority in North Dakota and South Dakota. There are no studies looking at what sociodemographic or biological factors may play a role in affecting outcomes and mortality of breast cancer (BC) among AIs in the United States. Our study compared the BC patterns, behavior, and survival of AIs living in the West North Central Region (WNCR) of the U.S (which includes ND, SD, MN, NE, IO, KS, MO) to the AI BC patients in the remainder of the country. Methods: We used the records of all AI BC patients diagnosed between the years 2004-2016 from The National Cancer Database participant user files. All analyses were conducted using SPSS software (version 25). Results: Records were available for 6,466 AI BC patients, 798 were in the WNCR. There was no difference between WNCR and other regions in the stage distribution, mean age at diagnosis, morphology, hormonal/HER2 status, tumor size, lymph node status, or second cancers. The WNCR patients had less private insurance, lived in zip codes with lower median income, had more co-morbidities, and traveled longer distances for care (p<0.001 for each). They had higher grade cancers (p<0.001) at diagnosis. The WNCR patients were less likely to have received radiation therapy (p=0.015) but more likely to have received chemotherapy (p<0.001) and hormonal therapy (p=0.009) and had longer inpatient stay days after surgery (p<0.001). Time to first treatment and first treatment within 90 days (88.0% vs. 79.7%, p<0.001) was significantly better in the WNCR than in other regions of the country. Five year mortality rate was higher (16.3% vs. 11.1%, p<0.001) and cumulative survival was lower (p<0.001) in the WNCR as compared to AIs in other regions of the country. Univariate/multivariate analysis failed to identify variables that could explain the differences in 5 year mortality or cumulative survival between WNCR and other regions. Conclusion:AIs with BC in the WNCR had worse 5 year mortality and cumulative survival as compared to AIs in other regions in the US. Our analysis could not identify variables that explained the differences in mortality or cumulative survival between WNCR and other regions. Citation Format: Anu G Gaba, Li Cao, Rebecca Renfrew, Deann Witte, Janet Wernisch, Denise Lutkemeier, Kristi Egland, Ross Crosby. Breast cancer patterns, behavior and survival among American Indians in the west north central region and the other regions of the U.S. [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-10.

PURPOSE:This study was designed to evaluate the effects of PD-1 inhibitor on lung tissue morphology and the immune system in a mouse model of radiation-induced lung injury (RILI) and to assess interactions between radiation therapy and PD-1 inhibition.METHODS:Twenty C57BL/6 mice were divided randomly into four groups of five mice each. Mice were treated with an anti-mouse PD-1 monoclonal antibody, whole thorax irradiation, both or neither. Lung tissue morphology and pathological changes were assessed by hematoxylin-eosin staining; lung fibrosis was assessed by Masson staining and analysis of hydroxyproline; CD3+, CD4+, and CD8+ T lymphocytes in lung tissues were detected immunohistochemically; and the concentrations of transforming growth factor-β1 (TGF-β1) and interleukin-6 (IL-6) in lung tissue were evaluated by cytokine multiplex analysis.RESULTS:Lung injury scores and indicators of pulmonary fibrosis were higher in mice administration whole thorax irradiation than in control mice. Inflammatory infiltrate scores, alveoli deformation scores, collagen volume fractions and hydroxyproline contents in lung tissues were all significantly higher in mice administered PD-1 inhibitor plus irradiation than in the other three groups. Similarly, the percentages of CD3+ and CD8+T cells and the concentrations of IL-6 and TGF-β1 in lung tissue were significantly higher in mice treated with radiation and PD-1 inhibitor than in the other groups. However, PD-1 inhibitor and irradiation interacted significantly only in the elevation of TGF-β1 level.CONCLUSION:Whole thorax X-ray irradiation in mice can cause pulmonary injury and fibrosis, which could be exacerbated by PD-1 inhibitors. Radiotherapy combined with PD-1 inhibitors may aggravate RILI by synergistically upregulating TGF-β1 expression, thereby affecting the immune-inflammatory microenvironment in the lungs.

Abstract Background The plant-based medicinal food (PBMF) is a functional compound extracted from 6 medicinal and edible plants: Coix seed, L. edodes, A. officinalis L., H. cordata, Dandelion, and G. frondosa. Our previous studies have confirmed that the PBMF possesses anti-tumor properties in a subcutaneous xenograft model of nude mice. This study aims to further investigate the effects and potential molecular mechanisms of the PBMF on the recurrence and metastasis of gastric cancer (GC). Methods Postoperative recurrence and metastasis model of GC was successfully established in inbred 615 mice inoculated with mouse forestomach carcinoma (MFC) cells. After tumorectomy, 63 GC mice were randomly divided into five groups and respectively subject to different treatments for 15 days as below: model control group, 5-Fu group, and three doses of PBMF (43.22, 86.44, 172.88 g/kg PBMF in diet respectively). The inhibition rate (IR) of recurrence tumor weights and organ coefficients were calculated. Meanwhile, histopathological changes were examined and the metastasis IR in lungs and lymph node tissues was computed. The mRNA expressions related to the canonical Wnt/β-catenin signaling pathway, epithelial-mesenchymal transition (EMT) and lymphangiogenesis were detected by RT-qPCR in recurrence tumors and/or lung tissues. Protein expressions of β-catenin, p-β-catenin (Ser33/37/Thr41), GSK-3β, p-GSK-3β (Ser9), E-cadherin, and Vimentin in recurrence tumors were determined by Western Blot. LYVE-1, VEGF-C/D, and VEGFR-3 levels in recurrence tumors and/or lung tissues were determined by immunohistochemistry staining. Results The mRNA, as well as protein expression of GSK-3β were up-regulated and the mRNA expression of β-catenin was down-regulated after PBMF treatment. Meanwhile, the ratio of p-β-catenin (Ser33/37/Thr41) to β-catenin protein was increased significantly and the p-GSK-3β (Ser9) protein level was decreased. And PMBF could effectively decrease the mRNA and protein levels of Vimentin while increasing those of E-cadherin. Furthermore, PBMF markedly reduced lymphatic vessel density (LVD) (labeled by LYVE-1) in recurrence tumor tissues, and mRNA levels of VEGF-C/D, VEGFR-2/3 of recurrence tumors were all significantly lower in the high-dose group. Conclusions PBMF had a significant inhibitory effect on recurrence and lung metastasis of GC. The potential mechanism may involve reversing EMT by inhabiting the Wnt/β-catenin signaling pathway. Lymphatic metastasis was also inhibited by PBMF via down-regulating the activation of the VEGF-C/D-VEGFR-2/3 signaling cascade.

Prior studies have shown that over a span of 20 years (1990-2009), breast cancer death rates in the U.S. have not significantly declined for American Indians (AIs) in comparison to the White population. Health insurance coverage contributes independently and positively to the health of individuals through the receipt of adequate preventive services and care for diseases such as breast cancer. To this end, the 2010 Medicaid Expansion as part of the Affordable Care Act (ACA) has extended the health insurance coverage eligibility to adults with incomes up to 133 percent of the federal poverty level. In this study, we examined whether Medicaid expansion resulted in the improvement of breast cancer management and prognosis for AIs relative to the White population. Methods: We abstracted information from the National Cancer Data Base (NCDB) for AI and White breast cancer patients diagnosed between the years 2004-2016 who lived in states that expanded Medicaid in January 2014, and those that did not expand Medicaid. Data on age, race, stage at diagnosis, insurance status, definitive treatment initiation within 30 days of diagnosis, and 3-year mortality was analyzed. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multiple logistic regression to determine the impact of race (White vs. AI), Medicaid expansion status, and pre- vs. post-expansion periods on breast cancer management and prognosis. All p-values are two-sided. Analyses were performed using SPSS software V25. Results: There were 1,465,103 newly diagnosed White and AI breast cancers between the years 2004-2016; 99.7% were Whites and 0.3% were AIs. Of these, 46.9% resided in states that expanded Medicaid in January 2014 and 53.1% in states that did not expand Medicaid; 73.8% were diagnosed in the pre-expansion period (January 2004-December 2013) and 26.2% were diagnosed in the post-expansion period (January 2014-December 2016). There was an increase in the proportion of early stage (0, 1) breast cancer diagnosis in the period 2014-2016 as compared to the period 2004-2013 (OR=1.434, 95% CI:1.159- 1.775; p = 0.001), and this increase was significantly greater for AIs than for Whites (6% vs 3%; p=0.027) in both expansion and non-expansion states. An independent chi-square analysis of AIs found that there was a significant increase of the early stage diagnosis in the expansion states during the post-expansion period (p=0.001). The proportion of uninsured declined in the period 2014-2016 as compared to the period prior (OR=0.331, 95% CI: 0.129- 0.850; p=0.022), more so in the expansion states (decrease from 1.4% to 0.8%), vs. non expansion states (decrease from 2.3% to 2.2%) (p=0.019); no difference in decline was found between Whites and AIs. The probability of getting first definitive treatment within 30 days of diagnosis declined more in states without Medicaid expansion (decrease from 54% to 43%) than in states with Medicaid expansion (decrease from 50% to 43%) (p=0.028) for both AIs and Whites; and the decline was more in Whites (decrease from 55% to 44%) than in AIs (decrease from 49% to 42%) from pre-expansion period to post-expansion period (p=0.018). The 3-year mortality rates did not show any significant relationship to race, expansion status, or the pre- or post-expansion periods. Conclusion: In patients newly diagnosed with breast cancer, the proportion of uninsured declined significantly with Medicaid expansion and the proportion of patients who received first definitive treatment within 30 days of diagnosis decreased significantly less in AIs and in states that expanded Medicaid under the Affordable Care Act. Medicaid expansion increased early breast cancer diagnosis in AIs; this effect was not seen in non-expansion states. Medicaid expansion did not affect 3-year mortality rate. Citation Format: Anu G Gaba, Li Cao, Rebecca Renfrew, Kristi A Egland, DeAnn L Witte, Janet Wernisch, Ross Crosby. Did Medicaid expansion under the Affordable Care Act narrow the gap between American Indians and Whites on breast cancer management and prognosis? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SS1-08.

目的：探讨原发性高血压（EH）、2型糖尿病（T2DM）患者心率变异性的临床特点。方法选取63例 EH 患者（EH 组）、70例 T2DM患者（T2DM组）和72例健康者（N 组）进行动态心电图（AECG）心率变异性（HRV）时域分析，监测 AECG 全部正常心动周期的标准差（SDNN），相邻正常 R-R 间期差值均方根（RMSSD），相邻 R-R 间期差值大于50 ms 的百分比（PNN50）。结果心率变异性时域指标 SDNN 组间比较显示，EH 组（107．9±33．2）ms、T2DM组（110．2±37．7）ms 明显均低于 N 组（122．3±31．9）ms，差异有统计学意义（P ＜0．05），而 EH 组和 T2DM组的 SDNN 比较，差异无统计学意义。同时三组间的RMSSD 和 PNN50比较，差异均无统计学意义。结论EH、T2DM中老年患者的 SDNN 减低，提示自主神经功能有病变。

目的:探讨护理干预对提高农村老年高血压患者的自我管理能力的影响,达到控制高血压的目的.方法:选择120例高血压患者,随机分为对照组和干预组各60例.对照组采用常规治疗、护理;干预组在常规治疗和护理基础上给予系统化健康教育及护理干预.结果:干预后患者服药依从性有明显提高,改变了不良的生活方式.结论:护理干预明显提高患者对疾病危险因素的认识,帮助患者建立良好的生活方式,从而提高患者的自我管理能力,降低高血压病并发症的发生.

Objective To investigate the neuropsychological features of different mild cognitive impairment (MCI) subtypes.Methods A neuropsychology battery was applied in this study.Seventy MCI participants were enrolled in the test and classified as:28 amnestic MCI ( aMCI),21 vascular MCI ( V-MCI),and 21 Parkinson' s disease MCI (PD-MCI).Forty six normal old people were also evaluated as control.Results First,there were significant differences in the CAMCOG-C and CAMCOG-C subscales of each MCI subtype compared with the normal control. aMCI patients showed significantly impaired orientation,language expression,recent memory,attention,calculation,abstraction and perception (t =4.580,5.150,3.053,4.070,5.918,2.121,2.952,3.175 ; all P ＜ 0.05).However,the ability of language comprehension,remote memory and execution were relatively reserved.V-MCI patients scored lower in the cognitive function of orientation,language expression,attention and execution compared with the normal control(t =2.974,3.165,4.216,3.197; all P ＜ 0.05),with no significant difference in memory,calculation,abstraction and perception.A boarder cognitive impairment was observed in PD-MCI patients who showed significantly impaired language expression,recent memory,remote memory,learning memory,attention and execution(t =4.433,3.065,3.821,3.447,5.344,0.348 ; all P ＜ 0.05).Second,aMCI (3.07 ± 0.81,11.07 ± 2.28 ) and PD-MCI (3.00 ± 0.89,11.33 ± 1.91 ) patients scored significantly lower in CAMCOG scores and CAMCOG subscales including recent memory and learning memory compared with V-MCI(3.52 ±0.87,12.48 ± 1.83;aMCI vs V-MCI:t =1.868,2.381,PD-MCI vs V-MCI:t =1.921,1.980 ; all P ＜ 0.05 ).The remote memory and execution function in PD-MCI were significantly impaired compared to the other two subtypes(PD-MCI vs aMCI:t =2.498,4.257; PD-MCI vs V-MCI:t =1.684,1.492 ;all P ＜ 0.05 ).Third,the GDS scores were different among the four groups. aMCI grouphad significant higher GDS score compared to the normal control group( t =2.850,P ＜ 0.05 ),while there were no similar changes in V-MCI and PD-MCI groups.Comparing different MCI subtypes with each other,aMCI and V-MCI groups had higher GDS scores than PD-MCI group.Conclusions The features of cognitive impairment in the 3 subtypes are all multiple domains.The characteristic impairment domains are memory in aMCI,executive function in V-MCI,and both memory and executive functions in PD-MCI.aMCI may show greater depression tendency compared to the other two subtypes.The different features in the subtypes of MCI may represent different pathophysiololgical changes in each MCI subtype.